Ischemic Stroke, AcuteENCHANTED3/MTNCT06352619
Third Enhanced Control of Hypertension and Thrombectomy Stroke Domain Within ACT-GLOBAL Adaptive Platform Trial
A study of Ischemic Stroke, Acute, run by The George Institute at 2 sites in 2 countries.
Trial summary
Several clinical trials have produced variable conclusions regarding the effects of intensive blood pressure (BP) lowering in post-EVT acute ischaemic stroke (AIS) patients. Although two trials indicate harm from very intensive target-based treatment (SBP <130 mmHg), the others neutral effects in the SBP range 140-160… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Stroke, Acute
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,000 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 11 Oct 2024to May 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years;
- Use of endovascular therapy (EVT) within 24 hours of symptom onset or last known well according to local guidelines;
- Sustained high systolic blood pressure ≥150 mmHg (2 readings <10 mins apart) within 3 hours after completion of EVT.
Who cannot join
- 1.Any definite contraindications to BP lowering treatment.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
Australia1 site, 1 recruiting
- Recruiting
The George Institute for Global Health
Sydney, New South Wales, 2000
Xiaoying Chen, PhD, +61 2 8052 4549, xchen@georgeinstitute.org.au
Craig Anderson, MD, PhD, +61 2 8052 4521, canderson@georgeinstitute.org.au
Canada1 site, 1 recruiting
- Recruiting
University of Calgary
Calgary, Alberta, T2N 1N4
Carol C Kenney, RN
Michael D Hill, MD
About this study
Official title: Third Enhanced Control of Hypertension and Thrombectomy Stroke Domain Within A Multi-faCtorial, mulTi-arm, Multi-staGe, Randomised, gLOBal Adaptive pLatform Trial for Stroke (ACT-GLOBAL_ENCHANTED3/MT)
Several clinical trials have produced variable conclusions regarding the effects of intensive blood pressure (BP) lowering in post-EVT acute ischaemic stroke (AIS) patients. Although two trials indicate harm from very intensive target-based treatment (SBP <130 mmHg), the others neutral effects in the SBP range 140-160 mmHg. The ENCHANTED3/MT domain of the ACT-GLOBAL platform trial aims to test different approaches to the treatment of elevated SBP in post-EVT AIS patients to find an optimal BP management strategy. ENCHANTED3/MT will randomize (1:1:1) up to 2,000 patients with SBP ≥150 mmHg post-EVT to conservative (no or minimal SBP reduction by 5-10mmHg or a target of 175-180mmHg if very-high baseline SBP [≥180mmHg]), moderate (SBP reduction by 10-20mmHg or a target of 160 ± 5, whichever is higher; no control if low-high baseline SBP [150-160mmHg]), or intensive (SBP reduction by 30-50mmHg or a target of 140±5 mmHg, whichever is higher) BP management.
Read the detailed description
ACT-GLOBAL is an international, multi-factorial, multi-arm, multi-stage, randomized, adaptive platform trial designed to simultaneously evaluate multiple treatments that may improve outcomes in stroke. One domain is ENCHANTED3/MT aiming to compare three BP lowering management strategies in post-EVT AIS patients with elevated SBP determine the best approach to improve functional outcome.
Background and Rationale - Different reperfusion status may have different BP patterns. A U-shaped correlation between post-EVT BP and outcomes may exist for patients who underwent recanalisation post-EVT. In addition, different BP lowering strategy may have different safety profiles and may potentially impact differently with regards to the risk of ICH for patients with reperfusion therapy.
The controversial overall clinical effect seen in clinical trials, including ENCHANTED2/MT, OPTIMAL BP, BP TARGET, BEST II and ENCHANTED, does not resolve the question over the optimal BP control strategy following EVT. The evidence is insufficient to make sensible recommendations over the optimal BP management in this important clinical group. Thus, the Blood Pressure Domain (ENCHANTED3/MT) aims to test different treatment approaches to the control of elevated SBP post-EVT in AIS patients to find the optimal BP management that leads to improved functional status with reduced ICH and no other harms.
ENCHANTED3/MT will randomize (1:1:1) up to 2,000 patients with SBP ≥150 mmHg post-EVT to the following three BP lowering management strategies.
Primary outcome is modified Rankin scale (mRS) at 90 days analysed with utility-weighted mRS using a Bayesian hierarchical linear model. Adaptive analyses will be conducted 3-monthly with prespecified statistical triggers for superiority, inferiority and equivalence.
- Conditions
- Ischemic Stroke, Acute
- Being tested
- Conservative SBP Control, Moderate SBP Control, Intensive SBP Control
- Keywords
- Blood Pressure, Endovascular Therapy, Ischemic Stroke
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conservative SBP ControlOther
No or minimal treatment; if there is a need to treat a patient with a very-high (>180 mmHg) baseline SBP, then the SBP reduction is 5-10mmHg or a target is 175-180 mmHg
Moderate SBP ControlOther
If the patient has a very high (>180 mmHg) or moderate high (160-180 mmHg) baseline SBP, SBP reduction is 10-20mmHg or a target of160±5 mmHg, which is higher; patients with low-high (150-160 mmHg) baseline SBP will not be treated
Intensive SBP ControlOther
SBP reduction by 30-50mmHg or a target of 140±5 mmHg, which is higher
| Study group | Role | What they receive |
|---|---|---|
| Conservative SBP Control | Experimental | Not described Receives: Other: Conservative SBP Control |
| Moderate SBP Control | Experimental | Not described Receives: Other: Moderate SBP Control |
| Intensive SBP Control | Experimental | Not described Receives: Other: Intensive SBP Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
modified Rankin scale
The mRS is a 7-outcome ordered categorical scale that assesses functional neurological status after stroke. It is not intended for use as a measure of historical functional status. It is well accepted as a standard outcome around the world in the stroke community, by patients and by regulatory authorities. The seven values and the clinical summary of the individual scores are summarized in the following:
0 = No symptoms
- = No significant disability; able to carry out all usual activities
- = Slight disability; can look after own affairs, but unable to carry out all previous activities
- = Moderate disability; require some help
- = Moderately severe disability; unable to attend to own bodily needs without assistance
- = Severe disability; bedridden and requiring constant nursing care and attention
- = Dead
Measured: 90 days
Secondary outcomes (9)
Excellent functional neurological outcome
Excellent functional neurological outcome refers to mRS 0-1. The minimum mRS is 0 (no symptoms) while the maximum mRS is 6 (death). The higher the mRS score is the worse outcome is.
Measured: 90 days
Independent functional neurological outcome
Independent functional neurological outcome refers to mRS 0-2. The minimum mRS is 0 (no symptoms) while the maximum mRS is 6 (death). The higher the mRS score is the worse outcome is.
Measured: 90 days
Health Related Quality of Life
Health Related Quality of Life is based on EuroQol 5 Dimension 5 Level (EQ-5D-5L). The EQ-5D-5L is a generic instrument for describing and valuing health. It is based on a descriptive system that defines health in terms of five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has five response categories corresponding to: no problems, slight, moderate, severe and extreme problems. The version of the instrument selected for the trial is interviewer administered either in-person, or by telemedicine or by telephone.
Measured: 90 days
Mortality
Mortality refers to the state of being not alive.
Measured: 90 days
Ordinal shift of 7 levels of modified Rankin scale
The modified Rankin scale (mRs) is an ordinal disability score of 7 categories (0 = no symptoms to 6 = dead). The distribution of mRs scores across its different strata in patients will be calculated.
Measured: 90 days
National Institute of Health Stroke Scale (NIHSS) score
The NIHSS is a standardized neurological examination score that is a valid and reliable measure of disability and recovery after acute stroke. Scores range from 0 to 42, with higher scores indicating increasing severity. The scale includes measures of level of consciousness, extra ocular movements, motor and sensory tests, coordination, language, and speech evaluations. The NIHSS will be administered at Baseline prior to each domain randomisation (unless specified otherwise in specific domains) and Day 2. The NIHSS as part of standard of care treatment may be used if an assessment was not done by clinical trial personnel.
Measured: 24-48 hours
Any intracranial haemorrhage (ICH)
Any ICH is defined as ICH of any type on brain imaging ≤2 days of treatment, identified by adjudicators.
Measured: 2 days
Symptomatic intracerebral haemorrhage (sICH)
Symptomatic ICH on follow-up imaging (up to 2 days from randomization) will be a reportable serious adverse event that is adjudicated centrally according to the standard approach of reporting symptomatic ICHs used in the Heidelberg classification.
Measured: 2 days
Serious Adverse Event (SAE)
As defined by the WHO International Drug Monitoring Centre (1994), an SAE is any untoward medical occurrence that is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; be an important medical event that may not result in death, be life-threatening, or require hospitalization, but may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes previously listed.
Measured: 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2024
- Study start11 Oct 2024
- Primary completionDec 2027 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ischemic Stroke, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The George Institute
- Sponsor type
- University, hospital or other
- Collaborators
- University of Calgary, Changhai Hospital
- Responsible party
- Sponsor
- Investigators
- Craig Anderson, PhD, Principal investigator, The George Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06352619
- Sponsor's protocol ID
- ACT-GLOBAL_AIS_03
- Acronym
- ENCHANTED3/MT
- Status last verified
- Jul 2026
- First submitted
- 2 Apr 2024
- Last updated
- 8 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: After this domain is completed, the archived de-identified limited dataset of randomized participants will be transmitted to and stored in the ACT-GLOBAL Data Repository, for use by researchers. Data can be shared after publication of the main results.
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Third Enhanced Control of Hypertension and Thrombectomy Stroke Domain Within A Multi-faCtorial, mulTi-arm, Multi-staGe, Randomised, gLOBal Adaptive pLatform Trial for Stroke (ACT-GLOBAL_ENCHANTED3/MT)
- ClinicalTrials.gov ID
- NCT06352619
- Acronym / sponsor ID
- ENCHANTED3/MT / ACT-GLOBAL_AIS_03
- Conditions
- Ischemic Stroke, Acute
- Keywords
- Blood Pressure, Endovascular Therapy, Ischemic Stroke
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- The George InstituteUniversity, hospital or other
- Collaborators
- University of Calgary, Changhai Hospital
- Study start
- 11 Oct 2024 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 8 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Several clinical trials have produced variable conclusions regarding the effects of intensive blood pressure (BP) lowering in post-EVT acute ischaemic stroke (AIS) patients. Although two trials indicate harm from very intensive target-based treatment (SBP <130 mmHg), the others neutral effects in the SBP range 140-160 mmHg. The ENCHANTED3/MT domain of the ACT-GLOBAL platform trial aims to test different approaches to the treatment of elevated SBP in post-EVT AIS patients to find an optimal BP management strategy. ENCHANTED3/MT will randomize (1:1:1) up to 2,000 patients with SBP ≥150 mmHg post-EVT to conservative (no or minimal SBP reduction by 5-10mmHg or a target of 175-180mmHg if very-high baseline SBP [≥180mmHg]), moderate (SBP reduction by 10-20mmHg or a target of 160 ± 5, whichever is higher; no control if low-high baseline SBP [150-160mmHg]), or intensive (SBP reduction by 30-50mmHg or a target of 140±5 mmHg, whichever is higher) BP management.
Detailed description
ACT-GLOBAL is an international, multi-factorial, multi-arm, multi-stage, randomized, adaptive platform trial designed to simultaneously evaluate multiple treatments that may improve outcomes in stroke. One domain is ENCHANTED3/MT aiming to compare three BP lowering management strategies in post-EVT AIS patients with elevated SBP determine the best approach to improve functional outcome.
Background and Rationale - Different reperfusion status may have different BP patterns. A U-shaped correlation between post-EVT BP and outcomes may exist for patients who underwent recanalisation post-EVT. In addition, different BP lowering strategy may have different safety profiles and may potentially impact differently with regards to the risk of ICH for patients with reperfusion therapy.
The controversial overall clinical effect seen in clinical trials, including ENCHANTED2/MT, OPTIMAL BP, BP TARGET, BEST II and ENCHANTED, does not resolve the question over the optimal BP control strategy following EVT. The evidence is insufficient to make sensible recommendations over the optimal BP management in this important clinical group. Thus, the Blood Pressure Domain (ENCHANTED3/MT) aims to test different treatment approaches to the control of elevated SBP post-EVT in AIS patients to find the optimal BP management that leads to improved functional status with reduced ICH and no other harms.
ENCHANTED3/MT will randomize (1:1:1) up to 2,000 patients with SBP ≥150 mmHg post-EVT to the following three BP lowering management strategies.
Primary outcome is modified Rankin scale (mRS) at 90 days analysed with utility-weighted mRS using a Bayesian hierarchical linear model. Adaptive analyses will be conducted 3-monthly with prespecified statistical triggers for superiority, inferiority and equivalence.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Conservative SBP Control | Experimental | Other: Conservative SBP Control |
| Moderate SBP Control | Experimental | Other: Moderate SBP Control |
| Intensive SBP Control | Experimental | Other: Intensive SBP Control |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age ≥18 years;
- Use of endovascular therapy (EVT) within 24 hours of symptom onset or last known well according to local guidelines;
- Sustained high systolic blood pressure ≥150 mmHg (2 readings <10 mins apart) within 3 hours after completion of EVT.
Key exclusion criteria (1 listed)
- 1.Any definite contraindications to BP lowering treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Conservative SBP ControlNo or minimal treatment; if there is a need to treat a patient with a very-high (>180 mmHg) baseline SBP, then the SBP reduction is 5-10mmHg or a target is 175-180 mmHg | Other | Conservative SBP Control |
| Moderate SBP ControlIf the patient has a very high (>180 mmHg) or moderate high (160-180 mmHg) baseline SBP, SBP reduction is 10-20mmHg or a target of160±5 mmHg, which is higher; patients with low-high (150-160 mmHg) baseline SBP will not be treated | Other | Moderate SBP Control |
| Intensive SBP ControlSBP reduction by 30-50mmHg or a target of 140±5 mmHg, which is higher | Other | Intensive SBP Control |
Primary outcome
modified Rankin scale
Time frame: 90 days
The mRS is a 7-outcome ordered categorical scale that assesses functional neurological status after stroke. It is not intended for use as a measure of historical functional status. It is well accepted as a standard outcome around the world in the stroke community, by patients and by regulatory authorities. The seven values and the clinical summary of the individual scores are summarized in the following: 0 = No symptoms 1. = No significant disability; able to carry out all usual activities 2. = Slight disability; can look after own affairs, but unable to carry out all previous activities 3. = Moderate disability; require some help 4. = Moderately severe disability; unable to attend to own bodily needs without assistance 5. = Severe disability; bedridden and requiring constant nursing care and attention 6. = Dead
9 secondary outcomes
Excellent functional neurological outcome
Time frame: 90 days
Independent functional neurological outcome
Time frame: 90 days
Health Related Quality of Life
Time frame: 90 days
Mortality
Time frame: 90 days
Ordinal shift of 7 levels of modified Rankin scale
Time frame: 90 days
National Institute of Health Stroke Scale (NIHSS) score
Time frame: 24-48 hours
Any intracranial haemorrhage (ICH)
Time frame: 2 days
Symptomatic intracerebral haemorrhage (sICH)
Time frame: 2 days
Serious Adverse Event (SAE)
Time frame: 4 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2026.
- ACT-GLOBAL Master Protocol RegistrationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. After this domain is completed, the archived de-identified limited dataset of randomized participants will be transmitted to and stored in the ACT-GLOBAL Data Repository, for use by researchers. Data can be shared after publication of the main results.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Craig Anderson, PhD principal investigator
The George Institute
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Ischemic Stroke, Acute, run by The George Institute at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xiaoying Chen, PhD (+61 2 8052 4549, xchen@georgeinstitute.org.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
modified Rankin scale (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.